tbuckley/cabot-search huggingface dataset:
Baseline characteristics, hospital outcomes, and palliative care utilization in leptomeningeal disease: A nationwide analysis.
Authors: Ekrem Turk, Khaldun Obeidat, Rafaella Litvin, Jay Vakil, Vaishali Deenadayalan, Ayobami Gbenga Olafimihan, Muhammad Bilal Ibrahim, Eda Sevim Boduroglu, Hafeez Shaka, Kunnal Batra
Journal: Journal of Clinical Oncology (2023)

e14004 Background: Leptomeningeal metastasis (LM) is a rare but devastating manifestation of cancer metastasis. Most solid tumors are known to cause LM, but the most common etiology is breast cancer and lung cancer. The incidence of LM has been increasing due to increased survival rates secondary to the improved systemic cancer treatment. Here we aim to explore the baseline characteristics, epidemiologic differences, palliative care utilization. and hospital outcomes of LM. Methods: Nationwide Inpatient Sample (NIS) database 2016-2019 was queried to determine adult hospitalized patients with LM and relevant cancers by using ICD-10 codes. We studied the racial and socioeconomic differences, palliative care utilization, length of stay (LOS), total hospital charges (THC), and all-cause mortality in cancer patients with and without LM. Multivariate logistic regression analysis was conducted to adjust for confounders. Results: There were 15,325 admissions with LM, 20% had lung cancer (LC) and 20.4% had breast cancer (BC). The prevalence of LM was 1.9% and 0.5%, respectively, in LC and BC patients. LM patients were younger (LC 63 vs 69; BC 56 vs 64 p&lt;0.001), more likely to be non-White, and more likely to have private insurance (37% vs. 19%, p&lt;0.001). LM admissions had significantly increased LOS and higher THC compared to other cohorts. BC or LC with LM was associated with significantly increased Palliative care consult rate ( LC 31% vs 16%; BC 29% vs 10% p&lt;0.001) compared to BC and LC without LM. Palliative care use was more common in the African American race. The all-cause mortality rate in hospitalizations with LM was increased compared to cancer without LM (LC 11% vs 8.6% p=0.008 aOR 1.41; BC 12.8% vs 4.5% p&lt;0.001 aOR 3.39). The white race (OR 0.6, p&lt;0.001) and Medicare (OR 0.58 p&lt;0.001) were associated with lower odds of mortality, while the Hispanic race (OR 1.43, p=0.042) and Medicaid (OR 1.39, p=0.041) were associated with higher odds of mortality among LM hospitalizations. Conclusions: While actionable mutations and targeted therapies are developing rapidly, therapeutic options for LM remain limited, with a median survival of 4-5 months. Palliative care remains essential for a better quality of life; hence further studies should be conducted to improve the utilization of palliative care and investigate racial and economic disparities in the utilization of such.
Racial differences in the utilization of MRI-guided biopsy before prostate cancer diagnosis.
Authors: Grace L. Lu-Yao, Krupa Gandhi, Nikita Nikita, Amy L Shaver, Swapnil Sharma, Scott W. Keith, Stephen J. Freedland
Journal: Journal of Clinical Oncology (2023)

5093 Background: Most low-risk prostate cancer (PCa) patients undergo active surveillance (AS). Compared with Whites, Blacks are more likely to opt for AS and suffer a higher risk of cancer progression while on AS. A primary concern of AS is the likelihood of missing clinically significant cancer. Transrectal ultrasound-guided biopsy is the most common method for diagnosing and grading PCa; however, this method often misses anterior PCa. Magnetic resonance imaging (MRI) allows clinicians to identify better and detect PCa; however, current guidelines on MRI-guided biopsy (MRI-GB) are inconsistent. This population-based study aimed to examine the utilization of MRI-GB 6 months before PCA diagnosis over time by race in the US. Methods: We used SEER-Medicare data to identify men diagnosed with PCa between January 1, 2012, to December 31, 2017, and excluded patients missing the date of diagnosis, being diagnosed at death, enrolled in HMO, or having no continuous A and B coverage six months before diagnosis. We used the CPT codes to identify prostate biopsy and MRI use. Multivariable logistic regression was used to evaluate racial disparity in MRI use six months before PCa. The model included covariates age, race, SEER region, marital status, state buy-in for Medicare (a poverty indicator), education, income, Charlson comorbidity index, and procedure (MRI) year. Results: Among 38,612 eligible men, MRI use six months before PCa diagnosis increased from 2012 to 2017 (3.2% to 24.3% among Whites, 1.8% to 14.2% among Blacks). Compared with Whites, Blacks were 38% less likely to receive pre-diagnosis MRI (OR=0.62, 95% CI 0.52-0.74). Besides race, having state buy-in for Medicare (OR=0.44; 95% CI 0.30-0.65) and geographic regions (Central vs. West OR=0.40; 95% CI 0.34-0.45) were strong predictors of lower utilization of MRI. Conclusions: The gap in the utilization of MRI may exacerbate racial disparities in PCa. Future studies are needed to identify potential barriers to adopting MRI for PCa workups.
Base-edited live microbiome therapeutics with target-aid -live biotherapeutic products (LBPS) with synergistic effects of anti-PD-1 antibodies in a syngeneic model of mice.
Authors: Ryo Okumura, Hitoshi Mitsunobu, Chiaki Ishii, Shoko Miyazaki, Taiga Tamiya, Francois Bernier
Journal: Journal of Clinical Oncology (2023)

e15104 Background: Base editing without DNA cleaving is a technique that introduces point mutations using enzymes that induce base conversions. Generally, only the point mutation occurs, achieving a high level of precision. Base editing can easily be applied to bacteria, for which DNA cleaving is often lethal. With Bio Palette's core technology of base editing, Target-AID, we can quickly achieve the required therapeutic effects by making pinpoint modifications to bacteria. Immune checkpoint inhibitors (ICIs) targeting CTLA-4, PD-1, or PD-L1 have shown outstanding therapeutic outcomes in various cancers. However, the therapeutic efficacy of ICIs-based immunotherapy has been limited. Recent studies have revealed that the human gut microbiome controls the efficacy of ICIs. Bacterial flagellin derived from Enterococcus spp. has been suggested to enhance immune responses to cancer through activation of TLR5 signaling (1). As a regulatory mechanism of flagellin secretion in Enterococcus spp, FliD, FlgK, FlgN, or FlgM are known as negative regulators. Thus, if the flagellar expression can be enhanced by making the negative regulator functionally deficient, it can be expected to increase the efficacy and response rate of ICIs when combination with a base-edited strain. Methods: As human TLR5 luciferase reporter assay, HEK293T cells were transfected with human TLR5-expression vector. BALB/cAnN mice (6–8 weeks’ old) were injected subcutaneously with 3 x 10 6 cells for murine colon cancer cell line CT-26. Six days post inoculation, the mice were randomized based on tumor volume into treatment and vehicle control groups (n = 10 per each group). Anti-mouse PD-1 antibody was dosed 5 mg/kg, q3d, iv, for up to 3 weeks either alone or in combination with each of various strains (1 x 10 9 CFU/mouse, po). Body weight and tumor size were routinely measured until endpoint. Results: To achieve the increased extracellular secretion of Flagellin, we created fliD dysfunctional strain because deletion of the flagellar cap component FliD was expected to promote extracellular secretion of Flagellin monomers. Comparing the wild-type strains we used, E. casseliflavus activated TLR5 compared to E. gallinarum. E. casseliflavus with a stop codon introduced into the fliD gene, BP5040 strain, was found to increase TLR5 activation by approximately 4.9-fold when compared to wild type strain. In vivo experiments indicated that antitumor effect was observed with BP5040 alone. Strikingly, a remarkable antitumor effect was also demonstrated when BP5040 was combined with an anti-PD-1 antibody. Conclusions: To achieve the desired therapeutic effect, we performed base editing without inserting foreign genes. As a result, BP5040 strain is found to be a potential candidate for the treatment of immuno-oncology, which was created using our LBP platform technology.
Exploring the efficacy of a continuous form of the histologic grade in prostate cancer prognosis prediction.
Authors: Tae-Yeong Kwak, JaeHeon Lee, Joonyoung Cho, Sun Woo Kim, Hyeyoon Chang
Journal: Journal of Clinical Oncology (2023)

e17105 Background: Adenocarcinoma of the prostate is the second most common type of cancer among men worldwide. The Gleason grading system remains the gold standard for evaluating the prognosis of prostate cancer by assessing the cancer morphology. However, the current discretized Gleason pattern regime limits the depiction of fine-grained histomorphological changes. We evaluated the efficacy of the algorithm-generated continuous histologic grade value in prostate cancer prognosis prediction. Methods: Whole-slide images of H&amp;E prostatectomy tissue, along with the follow-up data including new tumor event (NTE) and biochemical recurrence (BCR), were obtained for the cases diagnosed as prostate cancer during 2000-2013 from The Cancer Genome Atlas (TCGA) database. Cases with missing data were excluded, resulting in a total of 308 and 397 cases being used for the analysis of NTE and BCR, respectively. Our study utilized a deep learning-based algorithm that performs Gleason scoring as follows. First, it computes per-pixel likelihood values for each of the 4 classes: benign, Gleason 3, 4, and 5. Then, the per-pixel class with the highest likelihood value and the slide-wise ISUP grade group (GG-AI) is successively determined. We tweaked the algorithm to aggregate the likelihood-weighted Gleason grade assigned to each pixel into a continuous form of the histologic grade (c-HG). We compared the prognostic performance of c-HG with that of the original ISUP grade group in TCGA (GG) and that of algorithm-generated GG-AI in predicting the risk of NTE as well as BCR. The Cox regression analysis was conducted, setting the cases from one of three donating institutions (EJ, HC, KK) as the target, fitting the Cox model with the cases from the other institutions, and evaluating the fitted model on the target. Results: The median follow-up duration in months was 32 for NTE and 29 for BCR, respectively. The number of cases with NTE was 51, while the one with BCR was 82. The table presents the c-index values obtained from each institution for GG, GG-AI, and c-HG. Note that the number of cases in each institution is different for NTE and BCR, due to the different number of removed cases with missing data. c-HG showed the best average performance in both NTE and BCR risk predictions. It is also notable that c-HG showed a stable performance for varying institutions. Conclusions: We proposed an algorithm-based method of representing histologic grade as a continuous value, which may give better predictions in disease progression for prostate adenocarcinoma. [Table: see text]
Association of treatment regimens with quality of life and overall survival in patients with metastatic colorectal cancer in Peru.
Authors: Fernando Namuche, Jorge Leon
Journal: Journal of Clinical Oncology (2023)

e15617 Background: Colorectal cancer is a significant public health concern in Peru. Metastatic colorectal cancer patients have limited treatment options, and the prognosis is generally poor. In recent years, treatment regimens for metastatic colorectal cancer have evolved significantly, with the emergence of targeted therapies and immunotherapy. However, little is known about the impact of these treatment regimens on quality of life and overall survival in the Peruvian population. The objective of this study is to investigate the association between treatment regimens and quality of life and overall survival (OS) in Peruvian metastatic colorectal cancer patients. Methods: This retrospective study included patients diagnosed with metastatic colorectal cancer between 2010 and 2020 at the AUNA clinic. Patients were included if they received chemotherapy as first-line treatment and were followed up for at least 6 months. Quality of life was assessed using the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) questionnaire, which includes subscales for physical, social/family, emotional, and functional well-being, as well as colorectal cancer-specific concerns. Treatment regimens considered were: FOLFOX, FOLFIRI and others. Univariate and multivariate analyses were performed to identify factors associated with quality of life and overall survival. Results: A total of 193 patients were included in the study, and the median follow-up time was 14 months. The majority of patients were male (60.6%) and the median age was 57 years. The most common first-line chemotherapy regimens were FOLFOX (52.7%), FOLFIRI (23.5%), and capecitabine plus oxaliplatin (16.4%). The median overall survival was 14 months, and the 1-year overall survival rate was 52.8%. Patients treated with FOLFOX had significantly better quality of life scores than those treated with FOLFIRI or capecitabine plus oxaliplatin (p = 0.012). The difference in quality of life scores was most pronounced in the emotional and social/family well-being subscales. However, there was no significant difference in overall survival among the different treatment regimens (p = 0.344). Multivariate analysis showed that the presence of liver metastases and higher FACT-C scores were independent predictors of OS. Conclusions: Our study has shown that the choice of treatment regimen in Peruvian metastatic colorectal cancer patients can have a significant impact on their quality of life. Patients treated with FOLFOX as first line had better quality of life scores than those treated with FOLFIRI or capecitabine plus oxaliplatin, particularly in emotional and social/family well-being subscales. However, there was no significant difference in OS among the different treatment regimens. The presence of liver metastases and higher quality of life scores were found to be independent predictors of overall survival.
The impact of adjuvant platinum-based chemotherapy in early adult granulosa cell tumor of the ovaries: A meta-analysis of comparative studies.
Authors: Dinesh Keerty, Sindhu Priya Devarashetty, Philip A. Haddad
Journal: Journal of Clinical Oncology (2023)

5547 Background: Adult granulosa cell tumors (AGCT) are the most common type of malignant ovarian sex chord stromal tumors but only comprise 2 to 5 percent of all malignant ovarian neoplasms. Most granulosa cell tumors have an indolent growth pattern, and prognosis depends on the disease stage at diagnosis and the presence of residual disease after surgery. Though these tumors have metastatic potential, their tendency for late relapses is well documented. Despite the lack of supporting data, the National Cancer Centers Network recommends platinum-based adjuvant chemotherapy (AC) for Stage I with intermediate and high-risk features. Most studies have failed to show any benefit of AC with disease-free or overall survival. However, several of these studies were small, and some had short median follow-ups. Others included advanced stages and the juvenile variant of the disease. Therefore, we conducted this meta-analysis to evaluate the impact of AC on disease recurrence in a stage I enriched AGCT. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language, diagnosis of AGCT, studies with a preponderance of stage I, comparative studies of AC versus none, and studies that reported recurrence rates. Studies that had a preponderance of advanced stages or juvenile variants were excluded. A meta-analysis using the fixed effects and random effects models was conducted. Results: Seven retrospective comparative studies with a total of 500 patients were included. The average median age was 47 years, and the average median follow-up was 58 months. Approximately 79% of the sample were stage I, and 79% of stage I were IC. Most AC regimens used were BEP and EP, though it varied among the regions. Platinum-based AC in early-stage AGCT failed to impact recurrence rates compared to clinical observation (HR=1.39, 95%CI 0.86-2.25, I 2 =48%, p=0.18). Conclusions: This is the first meta-analysis to show that adding platinum-based adjuvant chemotherapy to surgery does not improve the recurrence rate in early AGCT. Therefore, in the absence of evidence supporting any benefit of AC in this disease, recommendations to use AC should be re-evaluated, especially since the risk of platinum-based AC with or without Bleomycin is well-documented and carry potentially serious side effects.
Early postoperative outcomes in stent vs stent-less ileal conduits after radical cystectomies.
Authors: Yash Shah, Rishabh Simhal, Kerith Ruoyao Wang, Zachary Prebay, Costas D. Lallas, Daniel P Simon, Leonard G. Gomella, Mihir S Shah
Journal: Journal of Clinical Oncology (2023)

e16612 Background: Placing stents at the ureteroileal anastomosis for radical cystectomy with ileal conduit (RCIC) diversion has been common practice for the vast majority of urologists. Recently, the practice has been called into question, as some institutions have shifted to not stenting their ileal conduits for patient comfort and convenience. In this study, we aim to investigate the difference in 30-day outcomes between patients who did and did not receive ureteroileal stents after RCIC. Methods: RCs performed between 2019-2020 were identified in NSQIP and the corresponding cystectomy-targeted database. Baseline demographics, comorbidities, and operative parameters were compared via Pearson’s chi-square and t-tests between stented and stent-less RCICs. Outcomes of interest included rates of urinary tract infections (UTIs), acute kidney injury (AKI), renal failure requiring dialysis, anastomotic leaks, ureteral obstruction, ureteral fistula formation, need for reoperation, and 30-day hospital readmissions. Outcomes were compared using Pearson’s chi-square. All statistical tests were two tailed, p&lt;0.05 considered significant. Results: 3,865 RCICs were identified, of which 446 (11.5%) were stent-less. There was no difference in baseline demographics, comorbidities, or operative parameters between the stented and stent-less group, with the notable exceptions that significantly more stent-less patients had robotic-assisted instead of open RCs compared to the stented group (33% vs 21%, p&lt;0.001), and significantly more stent-less patients were preoperatively on dialysis compared to the stented group (4.9% vs 0.5%, p&lt;0.001). There was no significant difference in 30-day rates of UTIs, AKIs, renal failure, anastomotic leaks, ureteral obstruction, ureteral fistula formation, need for reoperation, and readmissions between the stented and stent-less cohorts. Conclusions: Stent-less ileal conduits have recently emerged in popularity. This study represents the largest multi-institutional analysis comparing outcomes between traditionally stented and stent-less RCICs, and shows that there is no significant difference in outcomes. Given the added cost and patient discomfort of ureteroileal stents, this study may indicate that these stents may not play as significant of a role in preventing early complications as previously thought. These findings warrant further investigation.
The first cold atmospheric plasma phase I clinical trial for the treatment of advanced solid tumors: A novel 4<sup>th</sup> treatment arm for cancer.
Authors: Jerome Canady, Xiaoqian Cheng, Taisen Zhuang, Saravana Murthy, Aviram Nissan, Steven Gitelis, Lawan Ly, Olivia Jones, Mohammad Adele, Alan T. Blank, Cristina O'Donoghue, Kerstin Stenson, Karen O'Hara, Michael Keidar, Giacomo Basadonna
Journal: Journal of Clinical Oncology (2023)

e14596 Background: Local recurrence contributes to the poor prognosis for patients with Stage IV metastatic or recurrent solid tumors, despite advances in standard care. We report the clinical outcome of intra-operative Cold Atmospheric Plasma (CAP) combined with standard surgical procedures. Methods: The trial was a Phase I, multi-center, open-label, prospective, controlled study. Eligible patients undergoing surgery for advanced Stage IV metastatic or recurrent solid tumors were enrolled and preoperative treatments (neoadjuvant chemotherapy, immunotherapy, radiation, and primary surgery) were permitted. Participants were recruited from Rush University Medical Center in Chicago, Illinois and Sheba Medical Center in Tel HaShomer, Israel. Twenty patients (age 26-85 years) between March 2020 to April 2021 received intra-operative CAP treatment following surgical macroscopic tumor removal. The primary endpoint was safety, and the secondary endpoint was ablation of the local microscopic tumor bed without damaging the surrounding normal tissue. Results: Physiological data (blood pressure, pulse, body temperature, End Tidal CO 2 , and oxygen saturation) was recorded continuously throughout surgery. There were no significant changes (p &gt; 0.05) during intra-operative CAP treatment. One adverse event grade 3 or higher was reported but no adverse events were related to CAP. As of February 13, 2023, 10 patients died of their disease between 3-32 months. Kaplan-Meier overall survival curves show the interim 31-month rate is 24% (95% confidence interval [CI], 5.0 – 100.0%). Median survival is 23 months. For R0 patients, the Kaplan Meier local non-recurrence probability showed that the interim 28-month rate is 75% (n=8; 95% CI, 50.3 – 100.0%) as of February 13, 2023. Histological staining, TUNEL assay, and confocal imaging of the surgical margins revealed cancer cell death and no damage to the surrounding normal tissue. Primary culture of the tumor confirmed total cessation of cancer cell survival. Conclusions: CAP treatment in combination with surgery for high-risk stage IV solid tumors is safe and induces cancer cell death at the surgical bed without damaging non-cancerous tissue. The survival rate in R0-resected CAP-treated patients was significantly improved compared to R1 and R2 patients and local non-recurrence rate for R0 patients was noteworthy. Clinical trial information: NCT04267575 . [Table: see text]
Adverse Effects of Tracheostomy for Sleep Apnea
Authors: William A. Conway
Journal: JAMA (1981)

Tracheostomy resulted in dramatic and sustained improvement in the symptoms of 11 patients with upper airway sleep apnea. However, seven of eight patients who had a standard tracheostomy experienced tracheal granuloma or stomal stenosis. Tracheostomy was revised in five of these eight patients using cervical skin flaps. Three of the 11 patients had a skin flap tracheostomy as the original procedure. Only two of eight patients had tracheal complications after a skin flap procedure. Postoperative problems unrelated to the procedure included recurrent purulent bronchitis in four and psychosocial difficulties in ten. Permanent tracheostomy should be limited to patients with serious cardiopulmonary complications of upper airway sleep apnea. The cervical skin flap is the preferred procedure for long-term tracheostomy in these patients. (<i>JAMA</i>1981;246:347-350)